Subcutaneous amivantamab in recurrent/metastatic head and neck squamous cell cancer after disease progression on checkpoint inhibitor and chemotherapy: Preliminary results from the phase 1b/2 OrigAMI-4 study
Kevin J. Harrington, Ari J. Rosenberg, Muh Hwa Yang, J.L. Geiger, Marc Oliva, Myung‐Ju Ahn, Sun Min Lim, Will Ince, Aarti Bhatia, Siddharth Sheth, Bhumsuk Keam, Robert Metcalf, Joshua C. Curtin, Kiichiro Toyoizumi, Mark Wade, Emrullah Yilmaz, Priya Kim, Remy B. Verheijen, Sujay Shah, Mahadi Baig, Paul Swiecicki
Abstract
Overexpression of EGFR and MET occurs in a high proportion of recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Amivantamab, an EGFR-MET bispecific antibody with immune-cell directing activity, is approved in EGFR-mutated advanced non-small cell lung cancer and is being evaluated in phase 3 trials for other solid tumors. Cohort 1 of OrigAMI-4 (NCT06385080) enrolled adult participants with human papillomavirus-unrelated R/M HNSCC with disease progression on/after prior checkpoint inhibitor and platinum-based chemotherapy. Subcutaneous amivantamab was administered at 1600 mg (2240 mg for ≥ 80 kg body weight) on Cycle 1 Day 1 and 2400 mg (3360 mg for ≥ 80 kg body weight) thereafter. Primary end point was investigator-assessed objective response rate (ORR). As of July 1, 2025 (median follow-up, 3.5 months [range, 0-13.4]), 86 participants (median age, 63.5 years; 45 % Asian; 43 % White) received ≥ 1 dose of subcutaneous amivantamab. Subcutaneous amivantamab was well tolerated. Administration-related reactions were reported in 7 % (n = 6/86) of participants; no new safety signals were observed. In the efficacy population (n = 38; median follow-up, 8.3 months [range, 1.1-13.4]), confirmed ORR was 45 % (95 % CI, 29 %-62 %), median time to first response was 6.4 weeks (range, 5.7-18.3), and median duration of response was 7.2 months (95 % CI, 5.3-NE). The clinical benefit rate (responder or durable stable disease) was 76 % (95 % CI, 60 %-89 %). Median progression-free survival was 6.8 months (95 % CI, 4.2-9.0). Subcutaneous amivantamab as second-/third-line treatment among participants with R/M HNSCC demonstrated rapid and durable antitumor activity. The safety profile of subcutaneous amivantamab was consistent with previous studies.